3,3′-((3-Hydroxyphenyl)azanediyl)dipropionic Acid Derivatives as a Promising Scaffold Against Drug-Resistant Pathogens and Chemotherapy-Resistant Cancer

The synthesis and antimicrobial and anticancer activity of 3,3'-((3-hydroxyphenyl)azanediyl)dipropionic acid derivatives (<b>2</b>-<b>25</b>) against drug-resistant bacterial pathogens and FaDu head and neck cancer cells were investigated. The derivatives were synthesized through various methods, including esterification, hydrazinolysis, and condensation reactions. The compounds demonstrated structure-dependent antimicrobial activity, predominantly targeting Gram-positive pathogens. Compounds containing 4-nitrophenyl, 1-naphthyl, and 5-nitro-2-thienyl groups exhibited enhanced activity against <i>S. aureus</i> and <i>E. faecalis</i>. Additionally, compounds <b>5</b>, <b>6</b>, and <b>25</b> showed antiproliferative activity in cisplatin-resistant FaDu cells at low micromolar concentrations. The in silico modeling revealed that compound <b>25</b> interacts with the HER-2 and c-MET proteins. These compounds also induced significant oxidative stress in FaDu cells and demonstrated low cytotoxic activity in non-cancerous HEK293 cells. These results highlight the potential of <i>N</i>-aryl-substituted <i>β</i>-amino acid derivatives as promising scaffolds for the further development of novel amino acid-based antimicrobial and anticancer agents targeting drug-resistant pathogens and cancers.